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Decoding the CBCJill MacPherson DNP, APRN, FNP-BC, AOCNP

Disclosures

None

Objectives

• What are different types of blood cells• How do cells differentiate• Why is it important to know what each cell

line does• Common conditions diagnosed with CBC• When to refer

Hematology

• Prior to consulting Hematology• What do you want to know

• Be clear• Be specific

• Why• Helps to limit health care costs• Answers the question you want asked

Hematology

• What do we do?• Malignant hematologic conditions

• Multiple Myeloma• Acute Leukemias• Chronic leukemias• Myeloproliferative Disorders

Hematology

• What we do?• Non-Malignant conditions

• Anemias• Thrombocytopenia• Secondary polycythemia• Clotting disorders

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Hematology

• Website:• Hematology.org

• Click on education• Click on Resources for clinicians• Right hand side: Quick links:

• Blood: How I treat

So…About that CBC

Hematopoietic stem cells

• Hemo-blood• Poiesis-creation• What do stem cells do?

• Self-renewal• differentiation

Stem cell function

• Stem cells are multipotent• Long term (years)• Short term (months)

• 3 main functions• Generate new cells• Maintain function • Repair

Hematopoietic stem cells

• Self-renewal• Balancing act of 3 mechanisms

• Apoptosis• Cell death

• Self-renewal • Critical for regulating the number of stem cells

• Differentiation• Uncontrolled leads to hematologic malignant conditions

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White Blood Cells

• Myeloid cell line• Neutrophils• Eosinophils• Basophils• Monocytes

• Lymphoid cell line• lymphocytes

• T-cells• B-cells

Neutrophils

Neutrophils

• Normal Neutrophils• Approximately between 1.5X109/L-6.5X109/L • At birth- normal is approximately 12 X109/L

• Neutropenia• <0.5 X109/L [500/uL]

• Neutrophilia• >7.5 X109/L (adults)

Neutropenia• Inherited or acquired

• Severe aplastic anemia, Fanconi’s anemia• Congenital neutropenia• Benign ethnic neutropenia (BEN)

• Nutritional Deficiency• B12 Deficiency• Folate deficiency• Copper• Alcoholism

Neutropenia• Medications

• Cytotoxic drugs• Immunosuppressive medications

• Infection• Epstein-Barr virus• HIV• Hepatitis• Parasites• Bacterial infections

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Neutrophilia• Neutrophils

• Diurnal-peak late in the day• Peak in the afternoon

• Acute neutrophilia• Inflammation-stress, exercise• Infection• Surgery, GI hemorrhage• Thermal burns, electric shock• Systemic vasculitis• Myocardial infarction-more severe with neutrophilia• Pulmonary Embolism• Sickle cell anemia

Neutrophilia• Chronic neutrophilia

• Endotoxins• Glucocorticoids• Polycythemia Vera, Chronic Myelogenous Leukemia• Cigarette smokers• Rheumatoid arthritis• Osteomyelitis• Ulcerative colitis• Gout• Sweet Syndrome• Lung and gastrointestinal cancer-especially metastasis

Eosinophils and/or Basophilia

• Infection• parasitic

• Allergies• Cancer

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Eosinophils Infection

Basophils Monocytes

• Monocytes- 0.3X109/L-0.7X109/L• Phagocytes

• Kill microorganisms• ingest aged or damaged blood cells• Antimicrobial

• Inflammatory cytokines• Role in sepsis

• Wound healing participant

Monocytes• Monocytosis

• Endocarditis• Tuberculosis• Syphilis• CMML-type of myelodysplastic syndrome• Acute myelogenous leukemia

• Monocytopenia• Cytotoxic chemotherapy• Bone marrow failure • Hairy cell leukemia

Acute Myeloid Leukemia

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Lymphocytes• Lymphocytosis->4X109/L

• Chronic lymphocytic leukemia• Acute Lymphoblastic Leukemia• Lymphomas

• Secondary Lymphocytosis• Mononucleosis• EBV• CMV• Viral hepatitis• Dengue Fever• Bordetella pertussis

Lymphoma

Chronic Lymphocytic Leukemia Lymphocytes

• Drug induced Lymphocytosis• Dasatanib• Ibrutinib

Lymphocytes

• Lymphopenias-<1.0X109/L• Immunodeficiency• Measles• West Nile encephalitis• Herpes virus type 6 (HHV-6)• Herpes virus type 8 (HHV-8)• Autoimmune diseases

• Myasthenia Gravis, Systemic lupus erythematosus• Zinc deficiency

When to refer• No referral needed

• Mild asymptomatic neutropenia-explained by initial evaluation

• Most common cause of mild neutropenia is Benign Ethnic Neutropenia (BEN)

• Referral- days to weeks• Worsening ANC-not r/t BEN, rheumatoid condition or

hypersplenism• No improvement in nutritional interventions• Increased frequency of infections

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When to refer

• Refer in days• Hairy lymphocytes• Smudge cells• Unexplained lymphadenopathy/splenomegaly• Increased pancytopenia

• Immediate referral-hours• Blasts on blood smear• ANC less than 200 cells/microL or <0.2X109/L

So…About that CBC

Red blood cells• Hemoglobin

• Oxygen carrying capacity of whole blood• Expressed in g/dl or g/L

• Hematocrit• Cell volume• Expressed in percent

• Red blood cell count• Number of RBCs contained in a specified

volume of whole blood

Red blood cell indices• MCV-mean corpuscular volume

• Size of the patient’s red blood cell• Low, normal or elevated

• MCH-mean corpuscular hemoglobin• Average amount of hemoglobin in a red blood cell• Low MCH may indicate

• Hypochromia• thalassemia

Red blood cell indices• RDW-red cell distribution width

• Size• High=large variation in size

• Iron deficiency• Myelodysplastic syndrome (MDS)• Hemoglobinopathies• Transfusion recipients

• Low=homogeneity

Cycle of red blood cells

• Erythropoiesis• Erythropoietin-hormone is the regulator

• Produced mostly by the kidney• Not stored• It is secreted

• Reticulocytes tell if there is adequate erythropoiesis• Increased=problem

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Blood smear

Anemia

• 2 approaches• Kinetic

• Decreased RBC production• Increased RBC breakdown• Blood loss

• Morphologic• MCV• Reticulocyte count

Kinetic Approach

Iron deficiency Morphologic Approach

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Anemia from Nutritional Deficiencies

• Vitamin A deficiency-prevalent in school children in underdeveloped African countries• Decreased MCV• Decreased RBC concentration• Anisocytosis and poikilocytosis- on smear

• Vitamin B6 deficiency• Hypochromic microcytic anemia• Malabsorptive states• Dialysis• medications

Anemia from Nutritional Deficiencies

• Vitamin E deficiency• Caused by chronic fat malabsorption (Cystic Fibrosis)• Sickle cell disease-increase in irreversibly sickled

cells• Copper deficiency

• Malnourished children-• osteoporosis, flaring ribs, bony abnormalities

• Gastric bypass/bariatric surgery• Macrocytic anemia, neutropenia, ringed sideroblasts- can

mimic MDS.• Elevated zinc

B12 Deficiency Anemia

Anemia of chronic disease• Diagnoses

• Chronic inflammation• Chronic infection

• Lab values associated• Low serum iron• Low to normal transferrin• High to normal ferritin

• Why does this happen?• Inflammatory cytokines decrease erythropoiesis• Interleukin 6 increases hepcidin• Hepcidin blocks release of iron• =hypoferremia• Intervention-treat underlying disease and may be erythropoietin

Anemia

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Sickle Cell Anemia Alcoholism and Anemia• Alcoholism can cause:

• Nutritional deficiencies- folic acid• GI bleeding• Liver dysfunction• Hemolytic anemia• Hypersplenism

• What may be seen on the CBC• Mild macrocytosis• Iron deficiency• thrombocytopenia

Abnormal red blood cells Anemia Summary• Most diagnosed by morphologic approach

• Microcytic• MCV less than 80fl

• Iron deficiency• Thalassemia• Anemia of chronic inflammation

• Macrocytic• MCV greater than 100fl

• Alcoholism• Liver disease• Folate and B12 deficiency• MDS

Anemia Summary

• MCV between 80-100fl• Normocytic anemia

• Get peripheral blood smear or path review

• Questions to start asking:• Is the patient bleeding• Increase red blood cell destruction?• Bone marrow suppression?• Iron deficiency?• Folate or B12 deficiency?

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Polycythemia (erythrocytosis)

• Polycythemia is:• Increased hemoglobin concentration

• Greater than 16.5g/dl for men• Greater than 16.0g/dl in women

• Increased hematocrit concentration• Greater than 49% in men• Greater than 48% in women

Polycythemia

• Relative• Hemoconcentration

• Diuretics, vomiting, diarrhea• smoking

• Absolute• Increase in RBC mass

• Primary• Secondary

Polycythemia• Primary

• Mutation • Polycythemia vera• Myeloproliferative neoplasm

• Secondary• Physiologic response to hypoxia

• Pulmonary disease, obstructive sleep apnea, Carbon monoxide toxicity, residence at high altitude

• EPO secreting tumor• Hepatocellular carcinoma, renal cell carcinoma,

pheochromocytoma, fibroid tumors

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Evaluation of Polycythemia

• How urgent is it and what can I do before referral?

• Medical emergencies are a no-brainer• Cerebral vascular accidents• Chest pain

• Others related to the degree of polycythemia• Hematocrit of greater than 60, pruritis, abdominal fullness

vs• Hematocrit of 50 and asymptomatic

Evaluation of Polycythemia

• History• Hyper-viscosity Symptoms• Thrombosis or bleeding• Fever/chills/night sweats/weight loss/pruritus,

gout, splenomegaly• Dehydration• Cardiopulmonary disease

Evaluation of Polycythemia

• Social hx• Cigarette smoking• Exposure to carbon monoxide• Use of androgens• Use of erythropoietic agents

Evaluation of Polycythemia

• Physical exam• Dermatologic• Cardiopulmonary• Organomegaly

Lab testing for Polycythemia

• No specific guidelines at present• Pulse oximetry• LFTs• Renal panel• Urinalysis• EPO level

• Elevated=response to lack of oxygen or possible tumor

• decreased=polycythemia vera or MPN

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Referral

• Limit your differential prior to consultation• Trends, Trends, Trends

• Initial lab work to include:• Renal function panel• Liver function panel• Hepatitis serologies• Reticulocyte count• Iron studies to include serum, iron, TIBC, Ferritin• B12 and RBC folate• Spep/upep• TSH• Stool for occult blood

Referral

• Consult unexplained anemia with:• Other cytopenias• High LDH• Abnormal spep/upep• High reticulocyte count

Thrombocytopenia

• One of the most common referrals to hematology

• Normal platelet count 150-400 X109/L• Platelets have a life span of 7-10 days• One third of platelets stored in the spleen• Two thirds in the blood vessels

Thrombocytopenia classification

• Mild• Above 70X 109/L

• Moderate• 20-70 x109/L

• Severe• Less than 20 X109/L

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Thrombocytopenia• 5 classifications of thrombocytopenia

1. Pseudo thrombocytopenia• antiphospholipid antibodies

2. Impaired platelet production• ITP• Medications• Nutritional deficiencies

3. Increased platelet destruction• DIC

4. Abnormal distribution of platelets• Hypothermia, hypersplenism, infusions

5. Miscellaneous causes

Common Causes of thrombocytopenia

• Alcohol is one of the leading causes in Western Countries

• Systemic Lupus Erythematosus• Occurs in 20-40%

• Infection• Bacterial• Viral• Fungal

• Chronic liver disease-d/t splenic pooling• Medications

When to refer

• Before consultation:• Rule out clumping by requesting a path

review if available or send test for platelet clumps specifically

• Investigate for liver disease by:• Imaging• Substance abuse• Hepatitis B/C

• Consult- unexplained thrombocytopenia

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Thrombocytosis/Thrombocythemia Thrombocythemia/Thrombocytosis

• Thrombocythemia• Greater than 450 x 109/L

• Types of thrombocythemia• Reactive• Autonomic

Causes of Thrombocythemia

• Reactive Thrombocytosis• Anemia• Infection• Non-infectious inflammation• Splenectomy

Causes of Thrombocythemia

• Autonomic thrombocytosis• Clonal- means caused by a mutation

• Myeloproliferative neoplasms (MPN)• Essential thrombocythemia• Polycythemia vera• Myelofibrosis• Chronic Myeloid Leukemia• Myelodysplastic syndromes• Acute myelogenous leukemia

Thrombocythemia

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Evaluation of Thrombocythemia

• How quickly to refer depends on:• Patient condition• Degree of elevated platelets

• Asymptomatic• Outpatient• Platelets greater than 1 million should be

evaluated within days

Referral for thrombocythemia

• Reactive thrombocytosis• Generally doesn’t warrant immediate

hematology referral• Autonomic thrombocytosis

• Warrants a hematology referral • MPN• Thrombosis at an unusual site• Thrombosis in a young patient less than 45• Blasts on peripheral smear

Conclusion

• The Complete Blood Count has so much to offer in terms of diagnosing many medical conditions

• Being aware of diagnosis that affect the CBC can be cost-effective and limit referrals.

• This results in more accurate and concise referrals increasing the optimal patient experience.

The end

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ReferencesBerliner, N. (2019). Approach to the adult with unexplained neutropenia. In A. G. Rosmarin (Ed.),Uptodate. Retrieved August 1, 2019. https://www.uptodate.com/contents/approach-to-the-adult-with-unexplained-neutropenia

Coates, T. D. (2019). Approach to the adult with neutrophilia. In A. G. Rosmarin. (Ed.),Uptodate. Retrieved August 1, 2019. https://www.uptodate.com/contents/diagnostic-approach-to-the-patient-with-neutrophilia

Cuker, A., Steensma, D. P., Kemptom, C. L. & Nowakowski, G. S. (2016). American Society of Hematology Self-Assessment Program. (6th ed.). Washington, DC: American Society of Hematology

George, J. N. & Arnold, D. M. (2019). Approach to the patient with unexplained thrombocytopenia. In J. S. Tirnauer & Lisa Kunins (Eds.), Uptodate. Retrieved August 1, 2019.https://www.uptodate.com/contents/diagnostic-approach-to-the-adult-with-unexplained-thrombocytopenia

Kasper, D. L., Hauser, S. L., Jameson, J. L., Fauci, A. S., Longo, D. L., & Loscalzo, J. (2017). Harrison’s Hematology and Oncology. (3rd ed.) New York, NY: McGraw-Hill. https://hemonc.mhmedical.com/content.aspx?bookid=1924&sectioned=141417977

Kasper, D. L., Hauser, S. L., Jameson, J. L., Fauci, A. S., Longo, D. L., & Loscalzo, J. (2017). Harrison’s Hematology and Oncology. (3rd ed.) New York, NY: McGraw-Hill. https://hemonc.mhmedical.com/content.aspx?bookid=1924&sectioned=141418384

ReferencesKenneth, K., Lichtman, M. A., Prchal, J. T., Levi, M. M., Press, O. W., Burns, L. J., & Caliguri, M. (2016). Williams Hematology (9th ed.). New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com/content.aspx?bookid=1581&sectionid=137387736

Kenneth, K., Lichtman, M. A., Prchal, J. T., Levi, M. M., Press, O. W., Burns, L. J., & Caliguri, M. (2016). Williams Hematology (9th ed.). New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com/content.aspx?bookid=1581&sectionid=137387413

Kenneth, K., Lichtman, M. A., Prchal, J. T., Levi, M. M., Press, O. W., Burns, L. J., & Caliguri, M. (2016). Williams Hematology (9th ed.). New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com/content.aspx?bookid=1581&sectionid=94303394

Kenneth, K., Lichtman, M. A., Prchal, J. T., Levi, M. M., Press, O. W., Burns, L. J., & Caliguri, M. (2016). Williams Hematology (9th ed.). New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com/content.aspx?bookid=1581&sectionid=94303965

Kenneth, K., Lichtman, M. A., Prchal, J. T., Levi, M. M., Press, O. W., Burns, L. J., & Caliguri, M. (2016). Williams Hematology (9th ed.). New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com/content.aspx?bookid=1581&sectionid=137387736Kenneth, K., Lichtman, M. A., Prchal, J. T., Levi, M. M., Press, O. W., Burns, L. J., & Caliguri, M. (2016). Williams Hematology (9th ed.). New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com/content.aspx?bookid=1581&sectionid=94303965

ReferencesKenneth, K., Lichtman, M. A., Prchal, J. T., Levi, M. M., Press, O. W., Burns, L. J., & Caliguri, M. (2016). Williams Hematology (9th ed.). New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com/content.aspx?bookid=1581&sectionid=1080233

Kenneth, K., Lichtman, M. A., Prchal, J. T., Levi, M. M., Press, O. W., Burns, L. J., & Caliguri, M. (2016). Williams Hematology (9th ed.). New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com/content.aspx?bookid=1581&sectionid=101238861

Kenneth, K., Lichtman, M. A., Prchal, J. T., Levi, M. M., Press, O. W., Burns, L. J., & Caliguri, M. (2016). Williams Hematology (9th ed.). New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com/content.aspx?bookid=1581&sectionid=108068723

Kenneth, K., Lichtman, M. A., Prchal, J. T., Levi, M. M., Press, O. W., Burns, L. J., & Caliguri, M. (2016). Williams Hematology (9th ed.). New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com/content.aspx?bookid=1581&sectionid=1080810141

Kenneth, K., Lichtman, M. A., Prchal, J. T., Levi, M. M., Press, O. W., Burns, L. J., & Caliguri, M. (2016). Williams Hematology (9th ed.). New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com/content.aspx?bookid=1581&sectionid=108034325

Rosenthal, D. S. (2019). Evaluation of the peripheral smear. In S. Tirnauer. (Ed.),Uptodate. Retrieved August 1, 2019. https://www.uptodate.com/contents/evaluation-of-the-peripheral-blood-smear

ReferencesSchrier, S. L. (2019). Approach to the adult with anemia. In S. Tirnauer & Lisa Kunins. (Eds.),Uptodate. Retrieved August 1, 2019. https://www.uptodate.com/contents/diagnostic-approach-to-the-adult-with-anemia

Tefferi, A. (2019). Approach to the patient with polycythemia. In A. G. Rosmarin (Ed.), Uptodate. Retrieved August 1, 2019.https://www.uptodate.com/contents/diagnostic-approach-to-the-patient-with-polycythemia

Tefferi, A. (2019). Approach to the patient with thrombocytosis. In A. G. Rosmarin (Ed.), Uptodate. Retrieved August 1, 2019.https://www.uptodate.com/contents/approach-to-the-patient-with-thrombocytosis